Antithrombogenic Coating of Stents Using a Biodegradable Drug Delivery Technology

Abstract

SummaryTo reduce the thrombogenic properties of coronary artery stents, a biodegradable polylactic acid (PLA) stent coating with an incorporated thrombin inhibitor and a platelet aggregation inhibitor has been developed. In an ex vivo human stasis model, its effect on platelets, plasmatic coagulation and its release characteristics were studied using whole blood. Bare steel and bare gold-surface stents were compared to steel and gold-surface stents coated with PLA (30 kDa) containing 5% polyethyleneglycol (PEG)-hirudin and 1% iloprost, with an empty tube as control. Markers of activated coagulation (prothrombin fragment F1-2 and thrombin-antithrombin III complex, TAT), were assayed and the release of drugs from the coating was assessed by aPTT and collagen-induced platelet aggregation. Bare steel and gold stents were completely covered by a blood clot, and high levels of coagulation markers (F1-2 fragment and TAT) were detected. No differences in the thrombogenic properties were found between bare gold or steel stents. Coated stents were free of blood clots and only minor elevations of markers were detected. Release data from in-vitro studies over 90 days showed a gradual release of the drugs with an initial exponential release characteristic for PEG-hirudin, slow release of iloprost and a 10% degradation of the PLA carrier. This drug releasing biodegradable coating effectively reduced thrombus formation independent of the metallic surface.

Platelet responses and coagulation activation on polylactide and heparin–polycaprolactone‐L‐lactide ‐coated polylactide stent struts

“…20,21 Thrombotic occlusion of either polymercovered or polymeric stents has also been reported earlier in experimental models. 7,22,23 On the other hand, a number of studies have demonstrated that immobilized heparin and hirudin are able to improve the haemocompatibility of both SS and polymeric surfaces, [12][13][14]24 although the potential risk for heparininduced thrombocytopenia (HIT) and subsequent platelet activation are of continuing concern. Furthermore, heparin is known to have a dual role in blood coagulation.…”

Experimentelle Spondylodese der Schafshalswirbelsäule

“…Als Alternative stehen biodegradierbare Trägersysteme wie Polylaktide und Polyglykolide zur Verfügung [9,10,33,47,48]. Kürzlich wurde eine kalte Beschichtungstechnologie entwickelt, die es erlaubt, Implantate mit Trägermaterial zu überziehen [16,50]. In diese biodegradierbare Poly-(D,L-laktid) (PDLLA)-Beschichtung können biologisch aktive Substanzen (z.…”

“…Die Beschichtungstechnologie und die Eigenschaften der PDLLA-Beschichtung wurden bereits ausführlich beschrieben [16,50]. In Gruppe 3 und 4 wurden 150 µg rekombinantes humanes "bone morphogenetic protein-2" (rhBMP-2, Theodor-Boveri-Institut, Würzburg, Deutschland) in die PDLLA-Beschichtung integriert bzw.…”

“…Ein ideales Carrier-System sollte kontrolliert applizierbar sein, und vor allem eine kontinuierliche, definierte und lokale Applikation von Wachstumsfaktoren gewährleisten und dabei ohne Nebenwirkungen vollständig resorbierbar sein [7,12,13,18].Vor kurzem wurde eine biodegradierbare Poly-(D,L-laktid)-Beschichtung vorgestellt, die diese Anforderungen erfüllen könnte [16,50]. Dieses Beschichtungssystem ermöglicht die Beschichtung etablierter Implantate mit bioaktiven Substanzen [51].…”

Biodegradable poly(D,L‐lactide) coating of implants for continuous release of growth factors

“…4,25 In coronary stents, antithrombotic drugs were incorporated into a biodegradable PDLLA coating and led to significant reduction of local thrombotic reactions and restenoses of coronary vessels. 5,26 Gombotz et al described the controlled release of biologically active TGF-␤1 from a biodegradable poly(D,L-lactic-co-glycolic acid) and demineralized bone matrix. 27 The local application of recombinant human bone morphogenetic protein (rh-BMP-2) from collagen sponges or bio-absorbable poly(D,Llactide-coglycolide) (PLA/PGA) beads with osteopromotive membranes into rat mandibular defects shows a superior bone regeneration using PLA/PGA than a collagen carrier.…”